Medical Biotechnology Commons^™

Injuries In Manual And Mechanical Cpr, Macon Spruill, Malik Bangura

Physician Assistant Capstones, 2020-current

Objective: To compare the rate of injuries during cardiopulmonary resuscitation (CPR) using manual versus mechanical chest compressions with the Lund University Cardiopulmonary Assist System (LUCAS™).

Design: Systematic literature review

Methods: We investigated the use of 2 different CPR methods, manual and mechanical, in order to determine if one was more likely to cause injury in individuals during a cardiac arrest. PubMed searches were conducted using the terms “cardiopulmonary resuscitation,” “adverse effect,” “classification,” “method,” “mortality,” “statistical and numerical data,” “trends,” “complication,” “epidemiology,” and “etiology.” Studies were excluded if they took place before the year 2000, included individuals under 18 …

Use Of Cardiomems Hf Sensor In Management Of Nyha Class Iii Heart Failure, Trevor Andrunik, Anne Eady

Physician Assistant Capstones, 2020-current

Objective: Assess the ability of continuous pulmonary artery pressure monitoring via implantable CardioMEMs HF device to reduce hospitalization in New York Heart Association (NYHA) Class III heart failure patients over the age of 18. Design: Systematic literature review. Methods: Searches were conducted via PubMed and ClinicalTrials.gov using the single search term “CardioMEMs.” Inclusion criteria narrowed results to studies performed in the last 10 years, randomized control trials, cohort studies, and utilizing heart failure related hospitalization as the primary endpoint. Results: The current data unanimously asserts that the CardioMEMs HF device is effective at reducing heart failure related hospitalizations, with secondary …

A Computational Method For Estimating Trunk Muscle Activations During Gait Using Lower Extremity Muscle Synergies, Geng Li, Di Ao, Marleny M Vega, Mohammad S Shourijeh, Payam Zandiyeh, Shuo-Hsiu Chang, Valerae O Lewis, Nicholas J Dunbar, Ata Babazadeh-Naseri, Andrew J Baines, Benjamin J Fregly

Faculty, Staff and Student Publications

One of the surgical treatments for pelvic sarcoma is the restoration of hip function with a custom pelvic prosthesis after cancerous tumor removal. The orthopedic oncologist and orthopedic implant company must make numerous often subjective decisions regarding the design of the pelvic surgery and custom pelvic prosthesis. Using personalized musculoskeletal computer models to predict post-surgery walking function and custom pelvic prosthesis loading is an emerging method for making surgical and custom prosthesis design decisions in a more objective manner. Such predictions would necessitate the estimation of forces generated by muscles spanning the lower trunk and all joints of the lower …

An Auto-Inhibited State Of Protein Kinase G And Implications For Selective Activation, Rajesh Sharma, Jeong Joo Kim, Liying Qin, Philipp Henning, Madoka Akimoto, Bryan Vanschouwen, Gundeep Kaur, Banumathi Sankaran, Kevin R Mackenzie, Giuseppe Melacini, Darren E Casteel, Friedrich W Herberg, Choel Kim

Faculty, Staff and Students Publications

Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. Understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs, complementing drugs that target nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis. Alternate splicing of PRKG1 transcripts confers distinct leucine zippers, linkers, and auto-inhibitory (AI) pseudo-substrate sequences to PKG Iα and Iβ that result in isoform-specific activation properties, but the mechanism of enzyme auto-inhibition and its alleviation …

Artificial Intelligence In The Radiomic Analysis Of Glioblastomas: A Review, Taxonomy, And Perspective, Ming Zhu, Sijia Li, Yu Kuang, Virigina B. Hill, Amy B. Heimberger, Lijie Zhai, Shenjie Zhai

Electrical & Computer Engineering Faculty Research

Radiological imaging techniques, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are the standard-of-care non-invasive diagnostic approaches widely applied in neuro-oncology. Unfortunately, accurate interpretation of radiological imaging data is constantly challenged by the indistinguishable radiological image features shared by different pathological changes associated with tumor progression and/or various therapeutic interventions. In recent years, machine learning (ML)-based artificial intelligence (AI) technology has been widely applied in medical image processing and bioinformatics due to its advantages in implicit image feature extraction and integrative data analysis. Despite its recent rapid development, ML technology still faces many hurdles for its broader applications …

Advance Trends In Targeting Homology-Directed Repair For Accurate Gene Editing: An Inclusive Review Of Small Molecules And Modified Crispr-Cas9 Systems, Forough Shams, Hadi Bayat, Omid Mohammadian, Somayeh Mahboudi, Hassan Vahidnezhad, Mohsen Soosanabadi, Azam Rahimpour

Jefferson Institute of Molecular Medicine Papers and Presentations

Introduction: Clustered regularly interspaced short palindromic repeat and its associated protein (CRISPR-Cas)-based technologies generate targeted modifications in host genome by inducing site-specific double-strand breaks (DSBs) that can serve as a substrate for homology-directed repair (HDR) in both in vitro and in vivo models. HDR pathway could enhance incorporation of exogenous DNA templates into the CRISPR-Cas9-mediated DSB site. Owing to low rate of HDR pathway, the efficiency of accurate genome editing is diminished. Enhancing the efficiency of HDR can provide fast, easy, and accurate technologies based on CRISPR-Cas9 technologies. Methods: The current study presents an overview of attempts conducted on the …

Mechanical Understanding And Optimization Of Template Guided Core Needle Biopsy, Isaac Girgis

Honors Undergraduate Theses

Prostate cancer is the second highest cause of cancer related deaths among men. According to the diagnostic pathway for prostate cancer, a prostate biopsy is performed if an individual showed signs of lesions through high prostate-specific antigen (PSA) concentration or suggestive digital rectal exam (DRE) results. The core biopsy mechanism involves inserting a beveled needle into the organ and removing a cylindrical fragment of tissue. Many factors affect the histological quality of the sample, including fragmentation, needle deflection, and needle insertion velocity. If a biopsy core is not clinically viable, an alternative core will need to be taken, resulting in …

Effects Of Il-10 On Local Cell Populations And Functional Recovery Following Vml Injury, Zain Blackwell

Biomedical Engineering Undergraduate Honors Theses

Volumetric muscle loss (VML) injuries are prevalent in both military personnel suffering from battlefield related incidents, and civilians following severe motor accidents. Despite its prevalence, VML has no pro-regenerative clinical treatments in place to recover some of the functional capabilities of the damaged muscle. Free flap grafting, debridement of damaged tissue, and physical therapy are the only clinical standards available that offer little functional recovery benefits, even after years of consistent treatment. In this study, anti-inflammatory cytokine interleukin-10 in conjunction with autologous minced muscle was assessed as a possible treatment for VML injuries and its influences on cellular behavior within …

Novel Peptide Biomaterials For Enhanced Delivery Of Sirna Cargo For Treatment Of Ovarian Cancer, Timothy Samec

All Dissertations

Ovarian cancer is the 7^th leading cause of cancer related death and the 5^th most commonly diagnosed cancer among women. Primarily diagnosed in stage III or stage IV, aggressive treatment is necessary and involves surgical debulking and administration of systemic chemotherapeutics. Unfortunately, these strategies fall short in effectively treating ovarian cancer and many patients experience local disease recurrence, development of multidrug resistant tumors, regional or distant metastatic events, or a combination of the three. As such, there is a significant need for additional treatment options and methods of delivery to improve therapeutic efficacy and disease survivability.

RNA interference …

What Internal Variables Affect Sensorimotor Rhythm Brain-Computer Interface (Smr-Bci) Performance?, Alex J. Horowitz, Christoph Guger, Milena Korostenskaja

HCA Healthcare Journal of Medicine

In this review article, we aimed to create a summary of the effects of internal variables on the performance of sensorimotor rhythm-based brain computer interfaces (SMR-BCIs). SMR-BCIs can be potentially used for interfacing between the brain and devices, bypassing usual central nervous system output, such as muscle activity. The careful consideration of internal factors, affecting SMR-BCI performance, can maximize BCI application in both healthy and disabled people. Internal variables may be generalized as descriptors of the processes mainly dependent on the BCI user and/or originating within the user. The current review aimed to critically evaluate and summarize the currently accumulated …

What External Variables Affect Sensorimotor Rhythm Brain-Computer Interface (Smr-Bci) Performance?, Alex J. Horowitz, Christoph Guger, Milena Korostenskaja

HCA Healthcare Journal of Medicine

Sensorimotor rhythm-based brain-computer interfaces (SMR-BCIs) are used for the acquisition and translation of motor imagery-related brain signals into machine control commands, bypassing the usual central nervous system output. The selection of optimal external variable configuration can maximize SMR-BCI performance in both healthy and disabled people. This performance is especially important now when the BCI is targeted for everyday use in the environment beyond strictly regulated laboratory settings. In this review article, we summarize and critically evaluate the current body of knowledge pertaining to the effect of the external variables on SMR-BCI performance. When assessing the relationship between SMR-BCI performance and …

Iatrogenic Electrocautery Damage And Cellular-Based Corrosion Of Total Joint Arthroplasty Biomaterials, Kirsten Carol Miller

Theses and Dissertations (ETD)

Introduction. The number of patients undergoing a Primary Total Knee Arthroplasty (PTKA) has been increasing steadily each year. Of those PTKA patients, 20% report long-term pain and/or some functional deficit. Cobalt-Chromium-Molybdenum (CoCrMo) alloy is one of the most used materials in Total Joint Arthroplasty (TJA) implants due the material’s high strength, high corrosion resistance, and biocompatibility. The release of metal ions and potential occurrence of metallosis in TJA has been shown to be detrimental to the longevity of the implant. The mechanisms leading to this increase in metal ion concentrations have been up for debate, with some believing it is …

Transcatheter Mitral Valve Replacement And Repair Technology, Joel Thomas

Senior Honors Theses

The mitral valve is a two-cusp valve that is located between the left atrium and left ventricle of the heart. As blood flows from the lungs and enters the atrium, it must pass through this valve in one direction to enter the ventricle and be pumped out to the systemic circuit.

Mitral valve disease occurs when normal mitral valve function is impaired. Many different repair and replacement options exist. These options are contingent upon age and risk factors for patients. This paper focuses on the four main transcatheter mitral valve replacement devices that have limited human trials. It concludes that …

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Nih Funding For Vaccine Readiness Before The Covid-19 Pandemic, Anthony E. Kiszewski, Ekaterina Galkina Cleary, Matthew J. Jackson, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Rapid development of vaccines for COVID-19 has relied on the application of existing vaccine technologies. This work examines the maturity of ten technologies employed in candidate vaccines (as of July 2020) and NIH funding for published research on these technologies from 2000–2019. These technologies vary from established platforms, which have been used successfully in approved products, to emerging technologies with no prior clinical validation. A robust body of published research on vaccine technologies was supported by 16,358 fiscal years of NIH funding totaling $17.2 billion from 2000–2019. During this period, NIH funding for published vaccine research against specific pandemic threats …

Endmt Regulation By Small Rnas In Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress, Roberta Giordo, Yusra M A Ahmed, Hilda Allam, Salah Abusnana, Lucia Pappalardo, Gheyath K Nasrallah, Arduino Aleksander Mangoni, Gianfranco Pintus

Faculty, Staff and Student Publications

Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth …

Hyperpolarized Carbon-13 Magnetic Resonance Measurements Of Tissue Perfusion And Metabolism, Keith Michel

Dissertations and Theses (Open Access)

Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime.

In …

Modulation Of Ros In Nanosecond-Pulsed Plasma-Activated Media For Dosage-Dependent Cancer Cell Inactivation In Vitro, Chunqi Jiang, Esin Bengisu Sozer, Shutong Song, Nicola Lai, P. Thomas Vernier, Sigi Guo

Bioelectrics Publications

Dosage control of reactive oxygen and nitrogen species (RONS) is critical to low-temperature plasma applications in cancer therapy. Production of RONS by atmospheric pressure, nonequilibrium plasmas in contact with liquid may be modulated via plasma conditions including plasma treatment time and pulse voltage and repetition frequency. In this study, a terephthalic acid-based probe was used to measure hydroxyl radicals [OH_aq] in water exposed to plasma and to demonstrate that the OH_ag concentration increases linearly with treatment time. Fluorometric measurements of hydrogen peroxide concentration in plasma-activated water show a linear relationship between the H₂O₂ production …

Surgical Gps Proof Of Concept For Scoliosis Surgery, Austin Tapp, Michel Audette

Computational Modeling & Simulation Engineering Faculty Publications

Scoliotic deformities may be addressed with either anterior or posterior approaches for scoliosis correction procedures. While typically quite invasive, the impact of these operations may be reduced through the use of computer-assisted surgery. A combination of physician-designated anatomical landmarks and surgical ontologies allows for real-time intraoperative guidance during computer-assisted surgical interventions. Predetermined landmarks are labeled on an identical patient model, which seeks to encompass vertebrae, intervertebral disks, ligaments, and other soft tissues. The inclusion of this anatomy permits the consideration of hypothetical forces that are previously not well characterized in a patient-specific manner. Updated ontologies then suggest procedural directions throughout …

Examining Multiple Cellular Pathways At Once Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken

Faculty, Staff and Students Publications

Sensitive simultaneous assessment of multiple signaling pathways within the same cells requires orthogonal reporters that can assay over large dynamic ranges. Luciferases are such genetically encoded candidates due to their sensitivity, versatility, and cost-effectiveness. We expand luciferase multiplexing in post-lysis endpoint luciferase assays from two to six. Light emissions are distinguished by a combination of distinct substrates and emission spectra deconvolution. All six luciferase reporter units are stitched together into one plasmid facilitating delivery of all reporter units through a process we termed solotransfection, minimizing experimental errors. We engineer a multiplex hextuple luciferase assay to probe pathway fluxes through five …

Residues And Residue Pairs Of Evolutionary Importance Differentially Direct Signaling Bias Of D2 Dopamine Receptors, María E Terrón-Díaz, Sara J Wright, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The D2 dopamine receptor and the serotonin 5-hydroxytryptamine 2A receptor (5-HT2A) are closely-related G-protein–coupled receptors (GPCRs) from the class A bioamine subfamily. Despite structural similarity, they respond to distinct ligands through distinct downstream pathways, whose dysregulation is linked to depression, bipolar disorder, addiction, and psychosis. They are important drug targets, and it is important to understand how their bias toward G-protein versus β-arrestin signaling pathways is regulated. Previously, evolution-based computational approaches, difference Evolutionary Trace and Evolutionary Trace–Mutual information (ET-Mip), revealed residues and residue pairs that, when switched in the D2 receptor to the corresponding residues from 5-HT2A, altered ligand potency …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …

Towards An In Vitro Model Of Testing Osteoblast Cellular Function In Contact With Various Surfaces, Raheleh Miralami

Theses & Dissertations

Past studies have shown that the success of total joint replacements depends on the biocompatibility of orthopaedic materials, which can be improved by modifying the implant surface. However, the exact roles of these modifications and their effective mechanisms are poorly understood. The objective of this study was to develop and evaluate a model system to investigate the impact of nano-structured surfaces, produced by the ion beam-assisted deposition (IBAD) technique, on biomarkers of osteointegration using an in vitro model. The IBAD technique was employed to deposit zirconium oxide (ZrO₂), Titanium oxide (TiO₂), and Titanium (Ti) nano-films on …

Different Methodologies To Characterize And Diagnose Sickle Cell Disease In Both Developed And Developing Nations, Mohammed Alharbi

Dissertations, Masters Theses, Capstones, and Culminating Projects

Sickle cell disease (SCD) is a genetic blood disorder that causes the RBC to become sickle shaped due to a mutation in the β-globin gene encoding the protein hemoglobin. This disease causes reduced oxygen carrying capacity of RBC resulting in painful crisis, hemolytic anemia, and infection susceptibility. SCD affects around 100,000 individuals in USA alone and 14 million people globally. SCD affected individuals have high mortality rates. Early detection and constant monitoring of this disease is essential. The following review focuses on various methodologies that have emerged in the diagnosis of SCD. Also, low cost methods that can be easily …

Carcinogenesis In Prostate Cancer: The Role Of Long Non-Coding Rnas, John Aird, Anne-Marie Baird, Marvin C.J Lim, Ray Mcdermott, Stephen P. Finn, Steven G. Gray

Articles

LncRNAs appear to play a considerable role in tumourigenesis through regulating key processes in cancer cells such as proliferative signalling, replicative immortality, invasion and metastasis, evasion of growth suppressors, induction of angiogenesis and resistance to apoptosis. LncRNAs have been reported to play a role in prostate cancer, particularly in regulating the androgen receptor signalling pathway. In this review article, we summarise the role of 34 lncRNAs in prostate cancer with a particular focus on their role in the androgen receptor signalling pathway and the epithelial to mesenchymal transition pathway.

Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma And Induces Innate And Adaptive Memory Immune Mechanisms That Prevent Recurrence, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

Bioelectrics Publications

Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver. NPS induced specific increases in NKs and NKT-cells expressing CD8 and activation receptors CD314-NKG2D and CD161 (NK1.1) in the TME …

Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong

Bioelectrics Publications

Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O₂ plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response …

Tumor Cell Death After Electrotransfer Of Plasmid Dna Is Associated With Cytosolic Dna Sensor Upregulation, Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga N. Pakhomova, Loree Heller, Maja Cemazar

Bioelectrics Publications

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding …